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Prostate CancerPhase 3PRIMARY2NCT05154162

PSMA PET Additive Value for Prostate Cancer Diagnosis in Men With Negative/Equivocal MRI

A Phase 3 study testing PSMA PET/CT, Transperineal template prostate biopsy and Transperineal targeted prostate biopsy in people with Prostate Cancer, run by Peter MacCallum Cancer Centre, Australia at 6 sites in Australia.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This clinical trial will evaluate PSMA PET additive value for significant prostate cancer (sPCa) diagnosis in men with negative/equivocal MRI Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
PSMA PET/CT, Transperineal template prostate biopsy and Transperineal targeted prostate biopsy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
660 participants
Where
6 sitesAustralia
Study dates
2 Mar 2022to Aug 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must meet all the following criteria for study entry:
  • Males aged ≥ 18 years at the time of consent
  • No previously diagnosed prostate cancer
  • No previous prostate biopsy
  • Having undergone MRI within 9 months prior to randomisation and meet one of the following criteria:
  • PI-RADS 2 AND ≥1 red flag defined as:
Show all 16Show fewer
  • PSA density >0.1
  • Abnormal DRE
  • Strong family history (1 first degree relative or ≥2 second degree)
  • BRCA mutation
  • PSA >10
  • PSA doubling time <36 months
  • PSA velocity >0.75/year
  • PI-RADS 3
  • Intention for prostate biopsy
  • Willing and able to comply with all study requirements

Who cannot join

  • Patients who meet any of the following criteria will be excluded from study entry:
  • Having a PSA >20ng/ml
  • Having ≥ cT3 on DRE
  • Significant morbidity that, in the judgement of the investigator, would limit compliance with study protocol

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Australia6 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Royal Brisbane and Women's Hospital

    Brisbane, Queensland, 4006

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3000

  • Austin Health

    Melbourne, Victoria, 3084

  • Cabrini Health

    Melbourne, Victoria, 3144

  • St Vincent's Hospital

    Sydney, New South Wales, 2010

Other trials in Australia

About this study

Official title: Prospective Multi-centre Randomised Trial of the Additive Diagnostic Value of PSMA PET in Men With Negative/Equivocal MRI in the Diagnosis of Significant Prostate Cancer

This clinical trial will evaluate PSMA PET additive value for significant prostate cancer (sPCa) diagnosis in men with negative/equivocal MRI

Read the detailed description

This open label, phase III, multi-centre, randomised trial with a non-inferiority objective will evaluate the additive diagnostic value of PSMA PET for men with negative/equivocal MRI in the diagnosis of significant prostate cancer. Patients with a clinical suspicion of prostate cancer with PI-RADS 2 or 3 on MRI, meeting all the inclusion and none of the exclusion criteria will be randomised into experimental and control arms. Patients in the experimental arm would be subjected to Pelvic PSMA PET/CT, wherein the PSMA negative patients would not undergo biopsy as opposed to PSMA positive patients who will be subjected to Transperineal targeted prostate biopsy. Whereas patients in the control arm will only receive Standard of Care (SOC) with no additional imaging (PSMA PET) and will undergo Transperineal template prostate biopsy. The co-primary objectives are to assess (1) the percentage of men with sPCa in the experimental arm (transperineal targeted biopsy) compared to the control arm (transperineal template biopsy) defined as the presence of a single biopsy core indicating disease Gleason score (GS) 3+4(>10%)=7, grade group (GG) 2, and (2) the percentage of men who avoid transperineal prostate biopsy between both arms. The secondary objectives include determining the percentage of clinically insignificant PCa on targeted biopsy (experimental arm) versus transperineal template biopsy (control arm); estimating the difference in complications from transperineal prostate biopsy between both arms; the health economics impact between the experimental and control arms; estimating the mean difference between both arms in change from baseline in health-related quality of life (QoL); estimating the mean difference between both arms at each time point in generalised anxiety and cancer worry.

Conditions
Prostate Cancer
Being tested
PSMA PET/CT, Transperineal template prostate biopsy, Transperineal targeted prostate biopsy
Keywords
Prostate, Cancer, PSMA PET
Medical subject headings
Prostatic Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PSMA PET/CTDiagnostic test

    PSMA PET/CT (limited to the pelvis)

  • Transperineal template prostate biopsyProcedure or surgery

    Transperineal template prostate biopsies will be performed as per treating urologist's usual practice. No specific template for biopsy is prescribed for the purposes of the study. However, template sampling of the prostate is required, with a minimum of 12 cores, dependent on prostate volume. MRI will be available for any additional targeted biopsies required. Transperineal template biopsies must be labelled appropriately and sent for histopathological analysis.

  • Transperineal targeted prostate biopsyProcedure or surgery

    If the PSMA PET/CT is normal, transperineal prostate biopsy would be omitted If the PSMA PET/CT is abnormal, transperineal prostate biopsies would be performed targeting the MRI (done prior to study) and PSMA PET/CT images

Study groups in NCT05154162
Study groupRoleWhat they receive
ExperimentalExperimentalPelvic PSMA PET ± transperineal targeted prostate biopsy
Receives: Diagnostic Test: PSMA PET/CT; Procedure: Transperineal targeted prostate biopsy
ControlOtherNo pelvic PSMA PET + transperineal template prostate biopsy
Receives: Procedure: Transperineal template prostate biopsy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Presence of sPCa on prostate biopsy

    sPCa defined as Gleason score 3+4(>10%)=7, Grade group 2 Patients without biopsy (negative PSMA PET) are considered not to have sPCa.

    Measured: When histology results are available, at an expected average of 14 days post-biopsy

  2. Number of men who avoid transperineal prostate biopsy in the experimental arm

    In the experimental arm, if PSMA PET is negative, the patient does not have biopsy

    Measured: When the PSMA PET result is available, at most 28 days after randomisation

Secondary outcomes (9)

  1. Presence of insignificant prostate cancer (isPCa) on prostate biopsy

    isPCa defined as GS 3+3=6, GG 1 or GS 3+4(≤10%)=7, GG 2

    Measured: Within 3 months following randomisation

  2. Cost per quality adjusted life year

    cost-effectiveness analysis to assess the cost per quality adjusted life year (QALY) gained associated with the use of PSMA PET in addition to MRI compared with MRI alone for the diagnosis of sPCa. Importantly, this analysis will take into consideration the impact on costs and QoL associated with the hypothesised reduction in unnecessary biopsies arising from the improved accuracy of PSMA+MRI and the comparative interventions).

    Measured: Through study completion, estimated up to 2 years

  3. Health-related quality of life as measured by the EORTC QLQ-C30.

    Quality of life (QoL) will be assessed using QLQ-C30, which contains 30 items across five functional scales, three symptom scales, global health status, and six single items. Participant responses are collected using a four-point response scale ranging from 'Not at all' to "Very much". Higher scores indicate better QoL and function, while high scores for the symptom scale represent a high level of symptoms.

    Measured: Within 7 days of randomisation and every 6 months ± 30 days after randomisation

  4. Anxiety as measured by the GAD7 in the diagnosis of PCa.

    The generalized anxiety disorder Scale (GAD-7)14 is a 7-item, patient-rated questionnaire for screening and severity measuring of generalised anxiety disorder. The GAD-7 score is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of 'not at all', 'several days', 'more than half the days', and 'nearly every day', respectively, and adding together the scores for the seven questions. Scores of 5, 10, and 15 are taken as the cut-off points for mild, moderate and severe anxiety, respectively.

    Measured: Within 7 days following randomisation and every 6 months ± 30 days after randomisation

  5. Cancer worry in the diagnosis of PCa.

    The modified Cancer Worry Scale adaptation of Cancer Worry Scale is a 3-item questionnaire used in context of cancer worry in abnormal PSA levels in men participating in community screening program. The score is calculated by assigning scores of 1, 2, 3, and 4, to the categories 'not at all or rarely', 'sometimes', 'often', and 'a lot', respectively, and adding together the scores for the 3 questions. A final question asks about feelings of distress related to cancer risk.

    Measured: Within 7 days following randomisation and every 6 months ± 30 days after randomisation

  6. Number of biopsy cores

    Experimental arm: For patients with a positive PSMA PET, the images, the report and a simplified template will be made available to the treating urologist. Up to four identified lesions on PSMA PET and/or MRI will be targeted with each lesion having a minimum 5 cores.

    Control arm: Transperineal template prostate biopsies will be performed as per treating urologist's usual practice. No specific template for biopsy is prescribed for the purposes of the study. However, template sampling of the prostate is required, with a minimum of 12 cores,dependent on prostate volume.

    Measured: Within 3 months following randomisation

  7. Incidence of complications following transperineal prostate biopsy.

    Complications following biopsy will be assessed with a modified questionnaire validated in the PRECISION trial. Part 1 following randomisation is a 9 item questionnaire. Part 2 is a 23 item questionnaire administered at 3 and 6 months to assess complications from transperineal prostate biopsy. The following complications will be assessed via these forms: fever, blood in urine, blood in semen, blood in stool, acute urinary retention, erectile dysfunction, urinary incontinence, urinary tract infection and pain in the perineum.

    Measured: Within 7 days following randomisation and at 3 and 6 months after randomisation

  8. Incidence of erectile dysfunction following transperineal prostate biopsy

    The Sexual Health Inventory for Men (SHIM) is an adapted version of the 5 item International Index of Erectile Function (IIEF-5) score, developed to diagnose the presence and severity of erectile dysfunction. This validated questionnaire has a range of scores from 1 to 25, grading erectile dysfunction into 5 categories (none, mild, mild to moderate, moderate and severe).

    Measured: Within 7 days following randomisation and at 3 and 6 months after randomisation

  9. Number of men who have sPCa detected only with PSMA PET (MRI PI-RADS 2)

    Measured in the experimental arm in patients with positive PSMA PET and negative MRI (PIRADS 2). sPCa defined as Gleason score 3+4(>10%)=7, Grade group 2

    Measured: Within 28 days following randomisation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Dec 2021
  2. Study start2 Mar 2022
  3. Primary completion15 Dec 2025
  4. Study completionAug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Diagnosis
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
660 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05154162
Sponsor's protocol ID
20/043
Acronym
PRIMARY2
Status last verified
Mar 2026
First submitted
25 Oct 2021
Last updated
3 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: IPD may be shared upon request to the Sponsor.

Publications

  • Buteau JP, Moon D, Fahey MT, Roberts MJ, Ayati N, Papa N, Murphy DG, Kasivisvanathan V, Dhillon HM, Du YT, Dundee P, Foudoulis J, Hennes D, Hutton AC, Idiare J, Jack G, Kamath S, Lee SN, Lee SF, Lee ST, Leslie S, Levy SM, Link E, Mitchell C, Morigi JJ, Nguyen A, Olphert J, Patel MI, Pattison DA, Pearce A, Perera M, Thanigasalam R, Thomson A, Yaxley J, Thompson J, Hofman MS, Emmett L; PRIMARY2 Trial Investigators. Effect of [68Ga]Ga-PSMA-11 PET-CT in the diagnosis of prostate cancer in men with equivocal or clinically high-risk non-suspicious findings on multiparametric MRI (PRIMARY2): a multicentre, non-inferiority, phase 3, randomised controlled trial. Lancet Oncol. 2026 Jul;27(7):839-848. doi: 10.1016/S1470-2045(26)00120-8. Epub 2026 Jun 10.

    PubMed 42269655

  • Emmett L, Papa N, Hope TA, Fendler W, Calais J, Burger I, Eiber M, Barbato F, Moon D, Counter W, John N, Xue A, Franklin A, Thompson J, Rasiah K, Frydenberg M, Yaxley J, Buteau J, Agrawal S, Ho B, Nguyen A, Liu V, Lee J, Woo H, Hsiao E, Sutherland T, Perry E, Stricker P, Hofman MS, Kasivisvanathan V, Roberts M, Murphy D. Beyond Prostate Imaging Reporting and Data System: Combining Magnetic Resonance Imaging Prostate Imaging Reporting and Data System and Prostate-Specific Membrane Antigen-Positron Emission Tomography/Computed Tomography PRIMARY Score in a Composite (P) Score for More Accurate Diagnosis of Clinically Significant Prostate Cancer. J Urol. 2024 Aug;212(2):299-309. doi: 10.1097/JU.0000000000004010. Epub 2024 May 17.

    PubMed 38758680

  • Buteau JP, Moon D, Fahey MT, Roberts MJ, Thompson J, Murphy DG, Papa N, Mitchell C, De Abreu Lourenco R, Dhillon HM, Kasivisvanathan V, Francis RJ, Stricker P, Agrawal S, O'Brien J, McVey A, Sharma G, Levy S, Ayati N, Nguyen A, Lee SF, Pattison DA, Sivaratnam D, Frydenberg M, Du Y, Titus J, Lee ST, Ischia J, Jack G, Hofman MS, Emmett L. Clinical Trial Protocol for PRIMARY2: A Multicentre, Phase 3, Randomised Controlled Trial Investigating the Additive Diagnostic Value of [68Ga]Ga-PSMA-11 Positron Emission Tomography/Computed Tomography in Men with Negative or Equivocal Multiparametric Magnetic Resonance Imaging for the Diagnosis of Clinically Significant Prostate Cancer. Eur Urol Oncol. 2024 Jun;7(3):544-552. doi: 10.1016/j.euo.2023.11.008. Epub 2023 Dec 6.

    PubMed 38061976

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing PSMA PET/CT, Transperineal template prostate biopsy and Transperineal targeted prostate biopsy in people with Prostate Cancer, run by Peter MacCallum Cancer Centre, Australia at 6 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 3 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Presence of sPCa on prostate biopsy (time frame: When histology results are available, at an expected average of 14 days post-biopsy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05154162, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2026.

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